NIH expands program to crack medical mysteries

An effort at the U.S. National Institutes of Health (NIH) to diagnose mysterious diseases is undergoing a major expansion. Representatives of the Undiagnosed Diseases Program (UDP), administered by NIH’s National Human Genome Research Institute (NHGRI), announced today that six medical centers will join the program, forming a network of clinical sites to investigate intractable cases from patients around the country. The program aims to offer patients a long-awaited diagnosis—and sometimes treatment—while building up data for scientists studying the genetic basis of rare diseases.

The new sites—Baylor College of Medicine; the Harvard teaching hospitals (Boston Children's, Brigham and Women's, and Massachusetts General); Duke University; Stanford University; the University of California, Los Angeles; and Vanderbilt University Medical Center—will each receive a 4-year grant of roughly $7.2 million to participate. Like the NIH Clinical Center in Bethesda, Maryland, that served as a pilot site, the centers will host patients for about a week at a time, performing extensive clinical tests and genetic sequencing in search of an explanation for their symptoms.

Harvard Medical School in Boston, which received a $9 million award in January to act as “coordinating center,” will facilitate collaboration between researchers and will make patient data widely available through public repositories such as NIH’s database of Genotypes and Phenotypes, explained Anastasia Wise, director of NHGRI’s Division of Genomic Medicine, at a press conference today.

Since the program launched in May 2008, it has received applications from about 3200 patients, 750 of which were selected for study. “There has never been a shortage of referrals to the program,” UDP Director William Gahl said today. (Indeed, in 2011, the program temporarily stopped accepting applications to catch up on the flood of inquiries.) The program’s track record for medical sleuthing depends on how you define a diagnosis, Gahl said. Between 25% and 50% of cases are considered “resolved” based on a clinical, molecular, or biochemical diagnosis, while about a quarter are closed without an answer. “You can see that this is a difficult work, in which we sometimes fail,” he added.

The program now admits about 150 patients per year at the NIH Clinical Center, but plans to accommodate 50 per year at each of the seven sites by the summer of 2017.